Placebo Effects and Neuromodulation: Ethical Considerations and Recommendations.

Placebo-controlled trials are the gold standard of evaluating treatment efficacy in clinical research. Neuromodulation is emerging as an important treatment pathway for many neuropsychiatric conditions, and placebo control arms of these trials require careful design with unique considerations (e.g., sham devices that mimic active stimulation, blinding effectiveness). Inherent to placebo-controlled trials are ethical concerns, such as deception, and potential harm of not receiving the active treatment. In this article, we outline important ethical considerations of placebo-controlled trials across neuromodulation approaches and provide recommendations on how ethical principles can be adhered to going forward. We specifically address issues of autonomy and respect for persons, beneficence, and justice. Within the context of this ethical framework, we also discuss factors influencing placebo effects in neuromodulation, the importance of adequate blinding, and alternative trial designs that could be considered.

Effects of Season and Daylight Saving Time Shifts on Sleep Symptoms: Canadian Longitudinal Study on Aging.

BACKGROUND AND OBJECTIVES: There has been conflicting evidence regarding the association between seasonal changes and daylight saving time (DST) and sleep disorders. This topic is of particular interest currently because the United States and Canada are considering the elimination of seasonal clock changes. The aim of this study was to compare sleep symptoms among participants who were interviewed in different seasons and before/after the transition into DST and standard time (ST). METHODS: A total of 30,097 people aged 45-85 years taking part in the Canadian Longitudinal Study on Aging were studied. Participants completed a questionnaire on sleep duration, satisfaction, sleep-onset insomnia, sleep-maintenance insomnia, and hypersomnolence symptoms. Sleep disorders were compared between participants who were interviewed during different seasons and at different times of the year (DST/ST). Data were analyzed using χ2, analysis of variance, binary logistic, and linear regression tests. RESULTS: Among participants interviewed in different seasons, we found no difference in dissatisfaction with sleep, sleep onset, sleep maintenance, and hypersomnolence. Those interviewed in summer had slightly shorter sleep duration compared with those in winter (6.76 ± 1.2 vs 6.84 ± 1.3 hours). Participants interviewed 1 week before vs 1 week after DST transition showed no difference in sleep symptoms, except for a 9-minute decrease in sleep duration a week after transition. However, those who were interviewed a week after transition to ST compared with a week before reported more dissatisfaction with sleep (28% vs 22.6%, adjusted odds ratio [aOR] 1.34, 95% CI 1.02-1.76), higher sleep-onset insomnia (7.1% vs 3.3%, aOR 2.26, 95% CI 1.19-4.27), higher sleep-maintenance insomnia (12.9% vs 8.2%, aOR 1.64, 95% CI 1.02-2.66), and more hypersomnolence with adequate sleep (7.3% vs 3.6%, aOR 2.08, 95% CI 1.14-3.79). DISCUSSION: We found small seasonal variations in sleep duration but no difference in other sleep symptoms. The transition from DST to ST was associated with a transient increase in sleep disorders.

An evening light intervention reduces fatigue and errors during night shifts: A randomized controlled trial.

OBJECTIVE: Shift work causes circadian rhythms to misalign with the demands of the environment, which has been associated with sleep difficulties and cognitive impairments. Although bright light exposure during night shifts can improve circadian alignment, its implementation is often infeasible. Here, we tested whether light exposure in the evening, before the night shift, could improve fatigue, work performance, mood, and sleep. METHODS: Fifty-seven healthy nurses who worked full-time rapidly rotating shift schedules completed the study. In a mixed-design randomized controlled trial, participants completed a baseline observation period before following 1 of 2 interventions. The experimental intervention aimed to improve circadian alignment using evening light exposure and morning light avoidance; the control intervention aimed to improve alertness and reduce sleep disturbances by modifying diet. Every morning and evening for 30 days, participants completed measures of fatigue, work-related errors, sleepiness, mood, sleep duration, and sleep quality. RESULTS: Compared to the baseline observation period, the experimental intervention reduced errors by 67%, while the control intervention reduced them by only 5%. This reduction was partially mediated by fatigue; experimental participants reported less fatigue on work days than control participants (d = 0.25 [0.10, 0.38]). The experimental group also showed a small improvement in mood. Both groups showed reductions in fatigue (d = 0.29 [0.20, 0.36]) and sleepiness (d = 0.21 [0.12, 0.28]) as well as a small increase in sleep duration. CONCLUSIONS: Interventions based on evening light may be a feasible and effective strategy to reduce fatigue and errors in night-shift workers.

Emulating future neurotechnology using magic.

Recent developments in neuroscience and artificial intelligence have allowed machines to decode mental processes with growing accuracy. Neuroethicists have speculated that perfecting these technologies may result in reactions ranging from an invasion of privacy to an increase in self-understanding. Yet, evaluating these predictions is difficult given that people are poor at forecasting their reactions. To address this, we developed a paradigm using elements of performance magic to emulate future neurotechnologies. We led 59 participants to believe that a (sham) neurotechnological machine could infer their preferences, detect their errors, and reveal their deep-seated attitudes. The machine gave participants randomly assigned positive or negative feedback about their brain's supposed attitudes towards charity. Around 80% of participants in both groups provided rationalisations for this feedback, which shifted their attitudes in the manipulated direction but did not influence donation behaviour. Our paradigm reveals how people may respond to prospective neurotechnologies, which may inform neuroethical frameworks.

The effect of evening light on circadian-related outcomes: A systematic review.

Bright light exposure at night can help workers adapt to their shift schedules, but there has been relatively little research on evening light. We conducted a systematic review of studies that manipulated light exposure in the evening (broadly defined as 16:00-22:00) before real or simulated night shifts. Across the five eligible studies, evening light produced phase delays in melatonin, body temperature, and sleep propensity; it also improved sleep quality, sleep duration, memory, and work performance. There were mixed effects for mood, no changes in sleepiness, and no negative effects. The confidence in these results ranged from moderate for physiological markers of circadian phase delays to very low for mood. Future studies should compare the relative effectiveness and safety of evening versus night-time light exposure. Overall, the benefits of evening light for shift workers are tentative yet promising.

Developing a light-based intervention to reduce fatigue and improve sleep in rapidly rotating shift workers.

Over a quarter of employees in North America and a fifth of those in the European Union do shift work. Working these schedules increases fatigue, sleepiness, and errors at work. In the long term, it may also increase the risk of cardiovascular disease, gastrointestinal problems, and cancer. Some of these consequences may be partly due to circadian misalignment, in which sleep and activity patterns no longer align with one's circadian rhythms. Previous research has found that controlling light exposure can improve circadian alignment in individuals who work permanent night shifts. However, light-based interventions are rarely tested with rapidly rotating shift schedules, which include more than one type of shift within the same week (e.g., day shifts followed by night shifts). Further, many of the available interventions are seldom used in the workplace and may be less feasible in healthcare environments. In hospitals, the health and safety of both workers and patients can be compromised by increases in fatigue. We thus developed a practical intervention based on circadian and sleep hygiene principles to reduce some of the negative consequences associated with shift work. We then tested this intervention in a feasibility study of 33 nurses working rapidly rotating shifts. The study took place over two separate periods: the control (observation) period and the intervention period. Each period included two to four consecutive night shifts as well as the two days before and after those shifts. Nurses completed daily self-report questionnaires during both periods. During the intervention period, the nurses additionally followed a fatigue reduction plan. The plan involved 40 min of bright light exposure from a portable light box before night shifts, light avoidance using sunglasses after those shifts, and suggestions regarding the ideal times to sleep and nap. Results showed that nurses complied with the large majority of these recommendations. During the intervention period, nurses reported less fatigue, fewer work errors, better and longer sleep, and a more positive mood. Moreover, nurses with a preference for evenings (i.e., later chronotypes) reported the strongest benefits. Though more controlled studies are needed to assess causal mechanisms and long-term effectiveness, these promising results suggest that light-based interventions are feasible and may be effective at reducing fatigue in rapidly rotating shift workers.